Biotechnology, Pharmaceuticals

Profound pharmacological features are gained by the covalent linkage of polyethylene glycol (PEG) chains to protein drugs (pegylation). Most notably, life-time in vivo can be prolonged from minutes to hours. Current techniques of conjugation often yield inactivated proteins, especially with proteins and peptide drugs of lower molecular weight, leading to a limited use and a relatively low number of pegylated-protein drugs that are FDA-approved.

In view of this deficiency, Prof. Mati Fridkin and Prof. Yoram Shechter from the Weizmann Institute of Science developed a novel reversible pegylation technology which allows PEG-polypeptide conjugates to release the PEG-chains by non enzymatic spontaneous hydrolysis in physiological conditions. The hydrolysis of PEG conjugates proceeds at a slow continuous and predictable rate over many hours. Removal of the PEG-chain releases the parent peptide or protein in a non-modified and fully active form. In other words, inactive 'pharmacologically-silent’ pegylated protein/peptide in the circulatory system undergoes spontaneous hydrolysis as the PEG chain is detached and the released protein is fully reactivated, in a slow linear fashion with increased half life of 10 to 30 hrs.

This novel technology of reversible pegylation was tested in rodents in vivo with several pegylated drugs such as insulin, exendin-4, peptide YY 3-36, interferon α2, human growth hormone and atrial natriuretic peptide. In all cases, full biological responses, were achieved. Moreover, the given doses to obtain such responses were usually lower and for extended periods of time, indicating a significant elevation of the half life of the drug in the body.

Pegylation can now be applied to essentially all small peptide and protein drugs, which are short-lived species in vivo. This new development is expected to extend life-time, bioavailability and efficacy of presently used protein/peptide drug candidates marketed today (in billions of $US) as well as those in clinical development.

 

Meir Riba – Director
Guy Yachin – Director
Noam Lautman – Director
Ran Nussbaum – Director
 

 

The company is seeking a partnership with Biotech/Pharmaceutical companies who are interested in co-development of pegylated-drugs, and private equity investors who will sponsor the further technology and drug development process.